Hormones Flashcards
What nutrients contribute to proper production of thyroid hormones?
Iron, iodine, tyrosine, zinc, selenium, vitamin E, B2, B3, B6, C & D
Zinc & selenium increase conversion of T4 to T3
What factors can inhibit proper production of thyroid hormones?
Stress Infection Trauma Radiation, medications Fluoride (iodine antagonist) Toxins: pesticides, lead, mercury, cadmium Autoimmune disease - celiac
What can improve cellular sensitivity to thyroid hormones
vitamin A, exercise, zinc
What factors can increase conversion of T4 to rT3?
Stress, trauma, low-calorie diet, inflammation, toxins, infections, liver or kidney dysfunction, certain medications
What supplements can be given routinely in a hypothyroid patient?
Selenium (200-400mcg) Zinc (15-30mg) Vitamin D (2000IU) Vitamin A (2000IU) Iodine (150mcg) Iron (15-20 mg, in menstruating women; aim for ferritin of 50-100ng/mL)
What are some functions of cortisol?
Stimulates liver to convert amino acids to glucose and increase glycogen production
Mobilizes fatty acids into the blood
Increases coagulation
Suppresses parts of the inflammatory response
Prevents loss of sodium in the urine
Maintains resistance to stress, mood & emotional stability
What happens with chronic stimulation of cortisol production?
Stimulation of fat deposits Increases in blood pressure & blood sugar Increases in protein breakdown Bone demineralization Immune suppression Memory loss (hippocampus) Depression
What happens with chronic stimulation of catecholamine production?
Anxiety, depression
Increased CV risk factors - HTN, myocardial dysfunction
What are the 3 stages of Selye’s General Adaptation Syndrome? And the associated cortisol/DHEA lab findings?
Stage 1 - Arousal: cortisol & DHEA increase with episodic stress, but recovers to baseline. Asymptomatic, stimulated
Stage 2 - Adaptation: cortisol chronically elevated, DHEA declines; associated w/”stressed”, anxiety attacks, mood swings, depression
Stage 3 - Exhaustion: adrenal insufficiency w/low cortisol & DHEA; associated with depression & fatigue
What can disrupt hormonal balance?
Think STAINS
Stressors Toxins Antigens, allergens, adverse food reactions Inflammation Nutrition Inadequate Sleep
Genetics, nutritional insufficiency, insulin imbalances, poor diet, alcohol, smoking, food reactions, dysbiosis, hyperpermeability, B-glucoronidase, poor sleep, acute/chronic stress, adiposity, altered biotransformation, poor methylation, inflammation, infection, trauma, toxins
Which enzyme converts pregnenolone & progesterone towards sex hormone pathways?
What upregulates it?
17a-hydroxylase
Increased activity with hyperglycemia, hyperinsulinemia & PCOS
Which enzymes converts androstenedione and testosterone to estrone (E1) and estrone (E2), respectively?
What upregulates it?
What reduces it?
Aromatase
Increased activity w/alcohol, zinc deficiency, stress, hyperinsulinemia, cortisol, inflammation
Decreased w/lignans, soy, resveratrol, grape seed extract, proanthocyanidins, green tea, gingko, quercetin, vitamin C, stinging nettle, chrysin, metformin, beta sitosterol, progesterone
Which enzyme converts testosterone to dihydroxytesterone (DHT)?
What upregulates it?
What inhibits it?
5a-reductase
Upregulated by hyperinsulinemia
Inhibited by bee venom, Pygeum Africanum, stinging nettle root, soy
What enzyme is responsible for methylating 2-OHE1 and 4-OHE1?
What upregulates it?
What inhibits it?
Catechol-O-methyltransferase (COMT)
Upregulated by 5-MTHF, methylcobalamin, P5P, SAMe, Mg
Inhibited by soy, estradiol
What enzyme converts estrone (E1) to 2-OHE1?
What upregulates it?
What inhibits it?
Cytochrome 1A1
Upregulated by crucifers, berries, I3C, DIM, soy, flaxseed, quercetin, rosemary, exercise
Inhibited by OCPs, SAD, hops
What does PTSD stand for?
Production
Transport
Sensitivity
Detoxification/excretion
What is the order of treating hormone imbalances?
Adrenal -> thyroid -> sex steroids
What can cause testosterone deficiency? (ATMs)
Obesity, MetSx/DM2, sleep loss, stress, medications (chronic opioids, TCAs, glucocorticoids), cadmium, genetics (Kleinfelters XXY, Kallmann syndrome), tumors (prolactinoma), infiltrative diseases (hemochromatosis, amyloidosis), AIDS/HIV
Also prevalent in men with HTN and hyperlipidemia
What conditions can result from low testosterone?
Higher rates of MetSx, Type 2 DM Increased CV mortality Osteoporosis Sarcopenia Central obesity Cognitive decline (amyloid precursor protein dependence receptors on neurons and testosterone trophic effects) Low mood and energy ED
How to screen for low testosterone?
Birth history, maternal exposure, toxin exposure
Puberty & sexual development hx
Past or present major illnesses, nutritional deficiencies
Hx of depressed mood
Cardiometabolic disease
Changes in body characteristics (e.g gynecomastia)
What tests may be used to identify low testosterone?
Low total testosterone, early morning (ie <300ng/dL)
Also free T, SHBG, prolactin, LH, FSH to confirm and identify source of problem
What are interventions to increased testosterone production?
Weight loss, exercise (resistance + others)
Nutritional support w/vitamins A & D, Zinc
Optimize sleep (optimizes GH pulses and T in deep sleep)
Stress management
Cadmium detox w/Se, Zn, GSH, NAC, antioxidants; intestinal metal binders (silica, thiols)
How can we increase the sensitivity of androgen receptors?
Exercise - increase receptor density in skeletal muscle
Vitamin A
Manage E2 (as it increases dihydrotestosterone receptors in the prostate)
What can drive estrogen dominance?
ie high estrogen relative to low progesterone
Obesity & BMI, WHR (adipose tissue has aromatase and makes estrogen)
Upregulated aromatase
Environmental: Xenoestrogens/Endocrine disruptors, POPs, estrogens fed to cows
Caffeine
Alcohol
Gut dysbiosis
Stress, cortisol
Iatrogenic (OCP, HRT)
Impaired liver function
Nutrient deficiencies that impair ovarian and/or mitochondrial function
Lack of phytoestrogens
Too much sugar and refined starches (increases insulin and androgen production)
What can drive luteal phase dysfunction?
ie. low progesterone and luteal phase <11 days
Stress, low fat diet, energy deficit, excessive exercise, PCOS
What can drive hormonal insufficiencies in women?
Aging, menopause, premature ovarian failure, nutritional deficiencies
What can drive sub-optimal hormone metabolism?
ie. sub-optimal 2,4,16-OH-estrogen
SNPs (eg for COMT, GST, CYP enzymes) Poor diet, alcohol HRT Endocrine disruptors PCOS
Which estrogen metabolites are carcinogenic?
16a-OH-estrone
quinone (from 4-OH-estrone) - neutralized by GST enzyme
Note: 2-OH-estrone has minimal estrogenic effect and is the preferred metabolite; 16a-OH-estrone is similar estrogenic effect as estradiol
What are symptoms of low thyroid function?
Memory & concentration problems, headaches, migraines, constipation, gas/bloating, low libido, reactive hypoglycemia; SIBO symptoms
Fatigue, weight gain, cold, dry hair and skin, hair loss, edema, muscle and joint aches, depression;
Possibly low waking axillary temperature
What tests should be done for thyroid assessment?
TSH, T3, T4, RT3, TT3, TT3/RT3, FT3/FT4, Thyroid Antibodies (TPO, thyroglobulin)
Iron, RBC zinc, selenium: RBC selenium, whole blood glutathione, vitamin D, serum vitamin A, urinary morning fasting iodine spot, celiac screening, food sensitivities, toxic minerals (RBC)
What therapies are used for thyroid replacement?
Levothyroxin
Liothyronine
Standardized porcine thyroid glandular (4 parts T4, 1 part T3)
Compounded thyroid with various ratios of T4/T3
What are some environmental toxins associated with thyroid toxicity?
PCBs, BPA, triclosan, PBDEs have direct effects on thyroid receptor
Organochlorine pesticides, dioxins activate hepatic enzymes and reduce T4 half-life
Hg associated with elevated TgA
increase fluoride exposure? (especially with iodine deficiency)
Which thyroid enzymes require selenium?
What is recommended supplementation?
The selenoproteins: Deiodinases & glutathione peroxidase
Give: Selenomethionine 200ug daily
Note - selenium level is also inversely correlated with thyroid antibody and TSH levels
Which thyroid enzyme requires iron?
Heme-dependent thyroid peroxidase
Aim for ferritin above 100ug/L or 100ng/mL for symptomatic improvement
How does black cumin (nigella sativa) help with thyroid function?
1g BID decreased TPO antibodies, TSH and increased T4
Helps with thyroid gland repair, antioxidant, and immunomodulatory
What is the mechanism of action for LDN?
What is the recommended dosing for autoimmune thyroiditis?
Displaces endorphins from opioid receptors leading to a rebound effect which causes endorphin production increase, increase receptor sensitivity, increased endogenous opioid production, anti-inflammatory;
Also reduce thyroid antibodies, increase T4 to T3 conversion, reduce conversion to rT3
Start w/0.5-1.5mg/day and increase up to 3-4.5mg/day over the course of 2-4 weeks
What are potential side effects of LDN?
Insomnia, vivid dreams
Anorexia, nausea, diarrhea, anxiety
Muscle pain, drowsiness
Why might some patients feel better with combination thyroid replacement therapy (levothyroxine + liothyronine) vs mono therapy with levothyroxine?
Persistent symptoms might be explained by the inability of levothyroxine to restore T3 levels in serum and all target tissues.
Genetic polymorphisms in the deiodinase 2 enzyme
What is the case for desiccated porcine thyroid? What’s the case against?
Contains all different types of thyroid hormone (T4, T3, T2, T1), which may have beneficial effects. Also includes thyroglobulin, iodine and glandular tissue which might have beneficial effects
BUT, supra physiological dose of T3, possible potentiation of auto-immunity (theoretical, no evidence of this)
What foods can reduce absorption of thyroid replacement therapy?
Coffee, soy, calcium, aluminum antacids, ferrous sulfate, possibly grapefruit
What is optimum TSH level?
0.4-2/2.5
What is the cortisol awakening response?
Salivary cortisol quickly peaks 30-45minutes post-awakening (separate from the increase that occurs during second part of the night)
- believed to be influenced by stress anticipation and reflects capability to cope with acute stressor
High CAR is a pre-clinical biomarker indicative of early adrenal dysregulation
What is the significance of a flat cortisol curve?
Loss of resilience; inability of HPA axis to recover from challenges
Note if very low and flat - consider organic pathologies like Addison’s, pituitary pathologies
What are symptoms of chronically elevated cortisol?
Anxiety, depression, irritability, fatigue, night sweats, sleep disturbances, carb & sweet cravings, weight gain, hypertension, brain fog (hippocampal atrophy), compromised immunity
Note vicious cycle: increased cortisol - decreases gut immunity - increases food sensitivities - increases cortisol
What are conditions associated with chronically elevated cortisol?
IBS-C, insomnia, migraine, MELANCHOLIC depression, CFS, PMDD, anxiety, bipolar
How does chronically elevated cortisol contribute to depression?
Desensitization of glucocorticoid receptors resulting in the inability to return to resting conditions. Prolongs receptor activation and the downstream effects
What are characteristics of melancholic depression?
Anxiety, dread of the future, insomnia, lack of appetite,, worse in AM
Treatment-resistant depression associated with hyperactive HPA-axis and elevated cortisol; SSRIs decrease this
What are symptoms of chronic LOW cortisol?
Fatigue (especially morning or after a stressor), anxious, panic attacks, emotional paralysis, apathy, lack of motivation, memory loss, poor concentration, allergies, depression (worse in pm), low blood pressure, poor sleep (awakenings), cravings of salty, sour or spicy foods, anorexia, nausea, early onset menopause, decreased immunity
What are conditions associated with LOW cortisol?
Atypical depression, seasonal affective disorder, panic attacks, post-partum depression, GAD, BAD, CFS
Associated with CFS and ACEs in women
What is atypical depression and how is HPA axis dysfunction associated?
Sx: lethargy, hyperphasic, hypersomniac, diurnal (best in AM)
HPA-axis hypoactivity
What pattern of HPA/cortisol is associated with PTSD?
Hyperactive central CRH system, but underactive HPA axis; enhanced cortisol suppression
But often mixed - hypo, hyper-cortisolemia
What is CV prognosis of flatter cortisol curves?
Increased CVD mortality
What are signs of high adrenaline?
Weight loss, anxiety, hot flashes, cold (compensatory hypothyroidism), muscle wasting (if not exercising), bone loss
What are signs of high cortisol to look for on physical exam?
Depression/anxiety weight around midsection elevated cholesterol sx of high adrenaline body shape change (increased inflammation with android type + high cortisol, high insulin; extreme gynoid - estrogen imbalance)
What are hormonal consequences of cortisol “steal”?
Low progesterone, leading to anxiety, PMS, PMDD, hypoadrenalism, PCOS
What are PE findings associated with HPA dysfunction?
Orthostasis, iris can’t hold contraction when light shined in eye, Sergent’s white line (line drawn on abdomen stays white for several minutes instead of turning red), Rogoff’s sign (tenderness over adrenal glands), melasma, swollen ankles
What nutritional deficiencies are associated with taste bud atrophy?
B2, B3, B12, iron
What are tests used to assess HPA axis?
Serum: ACTH, DHEA-S, pregnenolone
Saliva: cortisol, DHEA, cortisol/DHEA ratio, melatonin, sex hormones
What are some basic supplements to consider for adrenal health and why?
B-Complex: B1 - antistress effects B5 1000-1500mg - supports adrenal release of cortisol & progesterone B6/P5P 50-100mg Biotin 1000mcg Folate 400-800cg B12
vitamin C 1-2g & antioxidant blend: vit C associated with Tyr, Trp, catecholamine and carnitine metabolism
Mg 400-600mg
Omega-3 FA 1-3g (blunts stress response)
Zinc 20-50mg (decreased w/stress; functions in immunity, oxidative stress, decreases neuroprotective GABA)
What botanical adaptogens/anxiolytics are preferred for alarm, Stage 1 adrenal response? (ie hypercortisolemia)
Ashwagandha, holy basil, L-theanine, 5-HTP, Passion flower, Valerian, kava kava, Rehmanna, Schisandra, polygala
What botanicals can be used for Stage 2 adrenal response? (ie resistance phase, early decompensation; hypercortisolemia)
Ashwaghana, rhodiola, cordyceps, Siberian ginseng (Eleuthero), SJW (affects genes associated with HPA), phosphatidylserine, dark chocolate (increases urinary excretion of cortisol and catecholamines)
L-lysine, l-arginine
What are some lifestyle and nutrition ways to modulate a hypercortisol state?
Stress reduction
Low GI diet, with frequent meals and no stimulants
Exercise, adequate sleep
MVI w/extra Mg, B complex, C and omega-3
Phosphatidylserine (lowers cortisol, helps w/sleep)
Rhodiola (has anti-fatigue effect + reduces stress response; can have stimulating effects, so start at 100mg and titrate), Siberian ginseng
DHEA as needed
What botanicals may be used for Stage 3 adrenal response? (ie exhaustion; hypocortisolemia)
Ashwagandha, Licorice, Rehmannia, cordyceps, Asian/panax ginseng
Licorice: decreases cortisol effects, increases aldosterone
What is the mechanisms behind hypotension associated with exhaustion phase?
Aldosterone levels may decrease from cortisol steal (chronically elevated), leading to orthostasis; Tx temporarily with increase in salt intake until underlying issues fixed
For what conditions has DHEA been found to be useful?
post-menopausal osteoporosis, SLE, psychiatric disease, sexual dysfunction
+ exercise - improves physical functioning in women
topical - for menopausal vaginal atrophy
What are the functions of testosterone?
Tissue growth and repair Male reproduction Biomarker for comorbid diseases Immune modulation Adipocyte growth inhibition Energy metabolism Lipid and CVD health
What are the subtypes of testosterone deficiency?
Classical schema:
Primary = decreased T, increased LH/FSH (testicular failure)
Secondary = decreased T, decreased or normal LH/FSH/GnRH (pituitary or hypothalamic failure)
But - this schema doesn’t account for majority of men having clinical and biochemical low T
Adult onset hypogonadism: part of secondary, but without a known medical cause (70% of with this have metabolic disease)
How is low testosterone associated with aging? (ie mechanisms)
- More comorbitidities = higher prevalence of T deficiency w/age
- SHBG levels rise with age, causing decrease in free T
- relative ratio of testosterone/estradiol decreases in some men
- age-related T levels decline partly due to primary testis failure; also GnRH decreases and GnRH/LH pulse amplitudes drop
- increased fat = leptin resistance = decreased GnRH release
- blunting of diurnal T rhythm with men age >45yo
